HLA-B44 subtypes and the chance of finding HLA compatible donor/recipient pairs for bone marrow transplantation: a haplotype study of 303 Italian families.
A total of 1176 HLA-A,B,DR haplotypes were reconstructed by typing 303 unrelated families referred to our laboratory during the last seven years for the search of HLA identical sibs in view of bone marrow transplantation. A total of 614 different three-locus haplotypes were found. Most of them (83.6%) were present only once or twice, whereas 24/614 (3.9%) were found 6-28 times each. HLA-B44 was present in 4 of these most frequent haplotypes. HLA-B44 has been implicated as the molecular target for bone marrow allograft rejection. Therefore, a better knowledge of the HLA-B44 haplotype relationships might prove useful for the programming of registries of unrelated bone marrow donors. Eighty five serologically defined HLA-B44 unrelated subjects, either one or both parents from the above families, were subtyped by a high-resolution sequence-specific oligonucleotide probing approach. Moreover, 34 unrelated potential donors recruited for those patients that did not find a suitable donor among their siblings were subtyped also for HLA-B44. B*4403, which accounted for 47/85 (55.3%) serologically defined B44 alleles, appeared in strong, statistically significant, linkage disequilibrium with HLA-A29, -A23 and -DR7. On the other hand, B*4402, which covered virtually all other B44 alleles, showed prevalent gametic associations with HLA-A2 and HLA-A24. The linkage disequilibrium between HLA alleles is the key for the low frequency of HLA-B44 mismatches in donors selected as HLA-A,B,DRB1 identical to patients waiting for unrelated bone marrow transplantation. If a given patient presents unusual haplotypes, the chance of finding HLA-B44 mismatches may be higher because of the presence of different haplotype relationships in the donors.
Mattiuz
P L
PL
Department of Clinical Physiopathology, University of Florence, Italy.
Di Paolo
E
E
Fossombroni
V
V
Menicucci
A
A
Pradella
F
F
Porfirio
B
B
Rombolà
G
G
D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D005787:Gene Frequency; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000145:classification / Q000235:genetics*; D059948:HLA-B44 Antigen; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D006684:HLA-DR Antigens